Leukemia

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Comment by mandy on October 13, 2010 at 2:54pm

Came across this evntually heartwarming Leukemia bone marrow donation story and had to share. Just goes to show how important it is to keep making donations as medical technology improves.

Just as the donor said, "You can do a small thing, and then ten years later has this huge effect."

Comment by PhoenixPat on July 23, 2010 at 6:59pm

Kudos to the CML Society of Canada for their new video on understanding PCR (Polymerase Chain Reaction) testing which educates, informs and empowers CML patients. http://www.youtube.com/watch?v=ZwgynKh6J5U

Comment by MVogel on June 22, 2010 at 10:37pm

How many people have CLL and/or have been pescribed IVIG? On behalf of a fairly large patient community, I am working on a documentary called "Dying For Help" and through my journeys I have met patients who have or are currently using IVIG for CLL and CML. The documentary is going to show patients across the country with rare, chronic and geneic disorders who are having problems with health insurance. Once these patients finally get a diagnosis and receive a prescribed treatment for their disease, not the symptoms, but the disease, they are often denied coverage for the therapy by insurance companies "deeming it medically not necessary" or "experimental". Instead these patients are treated for their symptoms with inexpensive medications such as steroids, antibiotics and certain chemo drugs. By the time they do receive IVIG often the disease is in its final stages. These patients are suffering slow, painful unneccessary deaths. Please go to www.dyingforhelp.com and watch the trailer and read about the documentary.

Comment by Marie on June 9, 2010 at 10:58am

Leukemia Health Activists!

As you may have noticed - we're holding our second Health Activist Meetup here in Boston & we'd like to know what you want to discuss with other Health Activists. Even if you won't be able to join us on the 24th, we hope you'll take a minute to let us know what topics would be of interest to you and your communities - please share your thoughts in the comment section on this blog post.

Hope to see you on the 24th!

Comment by PhoenixPat on June 7, 2010 at 7:09pm

The following articles from the New England Journal of Medicine are now available online at http://content. nejm.org/

They are also the basis for presentations this weekend at the American Society of Clinical Oncology (ASCO) meeting in Chicago.

1) Nilotinib versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia

Nilotinib at a dose of either 300 mg or 400 mg twice daily was superior to imatinib in patients with newly diagnosed chronic-phase Philadelphia chromosome–positive CML.

2) Dasatinib versus Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia

In patients with newly diagnosed chronic-phase CML, dasatinib, as compared with imatinib, induced significantly higher and faster rates of complete cytogenetic response and major molecular response.

The Journal also published an editorial on these developments:
http://content. nejm.org/ cgi/content/ full/NEJMe100443 0

Even Better Kinase Inhibitors for Chronic Myeloid Leukemia
Charles L. Sawyers, M.D.

The clinical success of imatinib in patients with chronic myeloid leukemia (CML), which was first reported 9 years ago,1 catalyzed a systemwide shift in the development of cancer drugs to include molecularly targeted therapies. According to one recent estimate, approximately 200 such drugs are now in the clinical-developmen t pipeline. First approved for interferon-resistan t CML, imatinib quickly became the standard of care in patients with newly diagnosed CML on the basis of the drug's remarkable efficacy (complete cytogenetic remissions in some 70% of patients) with minimal toxic effects when used as initial therapy.2 Success of that magnitude is rare in oncology.

But imatinib was the first drug of its kind — an early foray into the world of kinase inhibition when the properties of the ideal candidate drug were completely unknown. By today's standards, imatinib has relatively low potency and inhibits its target at micromolar rather than nanomolar concentrations. In addition, imatinib is susceptible to resistance through a large number of different mutations in the BCR-ABL target as a consequence of the way it binds the BCR-ABL kinase domain, an unforeseen issue at the time of its discovery.3

Two next-generation BCR-ABL kinase inhibitors, dasatinib and nilotinib, rapidly emerged as candidates for second-line CML therapy, largely on the basis of their activity against most, but not all, imatinib-resistant mutations in BCR-ABL.4,5 Both compounds are more potent than imatinib, and dasatinib differs further by binding BCR-ABL through a different conformational mechanism. As predicted from preclinical models, both drugs proved effective in patients with CML in whom imatinib had failed.6,7

In this issue of the Journal, two studies — one by Kantarjian et al.8 and the other by Saglio et al.9 — show that both compounds are superior to imatinib when used as initial therapy for CML. In these randomized phase 3 studies, both dasatinib and nilotinib were superior to imatinib after 1 year of treatment with respect to all end points that were measured. The findings include higher rates of complete cytogenetic remission, faster time to remission, and (most important) reduced rates of progression to accelerated phase or blast crisis. Some observers may argue that 1 year is too early in the comparison to claim victory in a disease with a much longer natural history, but early, sustained complete cytogenetic response is a validated surrogate marker for survival in CML on the basis of previous trials of interferon. Nonetheless, the differences between the two study groups must be revisited when longer follow-up is available.

Despite the superiority of dasatinib and nilotinib in these trials, it is important to recognize that resistance to these newer agents, as with imatinib, could become an issue. One key difference is that the spectrum of mutations in BCR-ABL that are capable of causing relapse is much more limited with these newer drugs. The most significant mechanism of treatment failure is likely to be the T315I mutation, known as the gatekeeper, which confers resistance to all three drugs. Although early attempts to overcome this mutation have been disappointing, recent clinical data with the experimental drug AP24534, which inhibits T315I BCR-ABL in models of CML,10 suggest that even tumors with this recalcitrant mutation can be successfully treated.11

Do the results reported in these trials presage the retirement of imatinib from CML therapy, forever enshrined in the history of oncology but no longer useful? The data regarding response and side effects in the two studies certainly make a strong case for dasatinib or nilotinib as first-line therapy over imatinib. All three drugs have outstanding safety profiles, but there are modest differences in side effects that might lead patients to switch from one drug to another. There have been associations with pleural effusions with dasatinib, biochemical changes in liver function and QT prolongation with nilotinib, and edema and muscle cramps with imatinib. Ironically, imatinib may survive the challenge on the basis of economic rather than scientific factors, since it could be available in generic form as early as 2014. With rising pressure to balance cost and efficacy, patients and payers may be forced to select the cheapest among three excellent treatment options.

These two studies cap a remarkable decade of progress in CML therapy and, for some, may raise the question of whether we have reached the limit of what we can hope to achieve. We know that imatinib induces a long-lasting remission but not a cure. Presumably, dasatinib and nilotinib will perform similarly, but with deeper, longer-lasting remissions. But the history of cytotoxic chemotherapy teaches us that remission — first seen in pediatric acute lymphoid leukemia and then in Hodgkin's disease and testicular cancer — is converted to a cure only through optimal deployment of combination therapy. The fact that CML remains dependent on BCR-ABL even after multiple rounds of BCR-ABL–inhibitor therapy suggests that combinations of two or three kinase inhibitors, when carefully selected to cover all known resistance mutations, could shut off all mechanisms of escape. In contrast to the empiricism that drove the development of combination chemotherapy, our precise molecular understanding of resistance in CML should rapidly point to the optimal combination of targeted agents. Furthermore, the lessons that we have learned from CML are likely to extend to other kinase-dependent cancers, such as gastrointestinal stromal tumors, lung cancers with mutant epidermal growth factor receptors, and BRAF-mutant melanomas.

Many observers have argued that the war on cancer, unleashed in 1971 with the National Cancer Act, was premature because we could not realistically expect progress in developing effective cancer treatments without understanding the root causes. Today our knowledge of the biologic underpinnings of cancer puts us in a very different place. The CML studies reported here give us new perspective on what is possible.

Comment by Alicia C. Staley on May 21, 2010 at 3:47pm

I posted The Philadelphia Chromosome and CML. Check it out if you have a chance!

Comment by Greg on May 18, 2010 at 10:02pm

Here’s an interesting read on some of the rationale used when developing cancer drugs. This piece discusses a drug initially used in treating metastatic melanoma that was later discovered to be efficacious in the treatment of acute leukemia. The abstract talks about the two schools of thought: “rational design,” in which the scientist starts with the disease and works backward, or “mass screening,” in which a scientist begins with a drug candidate and searches for diseases it might attack.

Read more: http://www.newyorker.com/reporting/2010/05/17/100517fa_fact_gladwel...

Comment by Alicia C. Staley on April 19, 2010 at 1:17pm

I just posted "What is CML?" What would you add to this resource listing?

Comment by Marie on April 19, 2010 at 11:57am

Just posted our Spotlight Interview with Annie from Living with CML! Be sure to check out her WEGO Health profile and welcome her to the community!

Comment by Mike Sheng on April 5, 2010 at 10:03pm

Sure, Thank you very much. :) Do you have a facebook page?

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